These results suggest that a considerable percentage of patients with a history of complete cleft lip and palate at our institution require orthognathic surgery. Factors that need to be considered in the interpretation of these results include the quest for improvement in the profile aesthetics; the fact that the Canadian health care system covers the costs of surgery, making it more accessible to the patients; and the inclusion in the above figures of patients who had orthognathic surgery solely for reasons of closure of previously ungrafted alveolar clefts and associated fistulae.

Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity.

No abstract

When used by cardiologists, HHU provides a more accurate diagnosis than physical examination for the majority of common cardiovascular abnormalities. The finding of no significant abnormality on HHU is also likely to result in less downstream testing and thus potentially reduce the overall cost for patients being evaluated for a cardiovascular diagnosis.

Choroidal neovascularization (CNV) is the major cause of vision loss in wet age-related macular degeneration (AMD). Current therapies require repeated intravitreal injections, which are painful and can cause infection, bleeding, and retinal detachment. Here we develop nanoparticles (NP-[CPP]) that can be administered intravenously and allow local drug delivery to the diseased choroid via light-triggered targeting. NP-[CPP] is formed by PEG-PLA chains modified with a cell penetrating peptide (CPP). Attachment of a DEACM photocleavable group to the CPP inhibits cellular uptake of NP-[CPP]. Irradiation with blue light cleaves DEACM from the CPP, allowing the CPP to migrate from the NP core to the surface, rendering it active. In mice with laser-induced CNV, intravenous injection of NP-[CPP] coupled to irradiation of the eye allows NP accumulation in the neovascular lesions. When loaded with doxorubicin, irradiated NP-[CPP] significantly reduces neovascular lesion size. We propose a strategy for non-invasive treatment of CNV and enhanced drug accumulation specifically in diseased areas of the eye.

No abstract

Endothelial cell barrier function plays a prevalent regulatory mechanism for the integrity and homeostasis of blood vessels and modulates angiogenesis and immune responses. Cell adhesion molecules (CAMs) play a central role in the barrier function of endothelial cells. Although immunoglobulin containing and proline-rich receptor-1(IGPR-1) was recently identified as a novel CAM expressed in endothelial cells, the molecular mechanisms underlying the function of IGPR-1 in endothelial cells remain uncharacterized. In this report, we investigated the role of IGPR-1 in endothelial cell barrier function and the molecular mechanism of its activation in endothelial cells. We demonstrate that IGPR-1 is localized to endothelial adherens junctions, and through trans-homophilic dimerization regulates endothelial cell-cell adhesion and barrier function. Trans-homophilic dimerization of IGPR-1 stimulates phosphorylation of serine 220 (Ser220), which is required for IGPR-1 to regulate endothelial barrier function and angiogenesis. Moreover, IGPR-1 chimera, which mimics the trans-homophilic dimerization of IGPR-1, induced a sustained phosphorylation of Ser220 upon stimulation with a ligand. Coordinated dimerization of IGPR-1 and its homophilic interaction modulates its adhesive function and Ser220 phosphorylation. This adhesive function of IGPR-1 contributes to the barrier function of endothelial cells.

No abstract